The objective of this study is to develop and test a method for measuring lung circulatory transport properties (pulmonary blood flow, capillary permeability, extravascular lung water) which does not need radioactive tracers. The specific goals of the research are as follows: 1) identify materials which have optical properties that will allow their measurement in tracer concentrations in whole blood; 2) design a computerized multi- channel optical analyzer capable of measuring optical density in flowing blood; 3) perform calibration studies, studies of the effects of light scattering and comparisons of optical and radioactive tracer curves with an in vitro mixing system; and 4) compare the optical tracer curves to radioisotope tracer curves with in vivo indicator-dilution studies in isolated, perfused dog lung preparations under baseline conditions and after lung injury. Published work by others and preliminary data from this laboratory indicate that the optical properties of 1,2-propanediol, deuterated water (D2O), indocyanine green-labelled plasma protein (ICG) and sulfhemoglobin labelled erythrocytes (SHb-rbc) have characteristics which will allow their identification as constituents of a single mixture. These materials will act as nonradioactive probes of red cell and plasma flow (SHb-rbc and ICG), capillary permeability (1,2-propanediol), and extravascular lung water (D2O) in the lung microcirculation. Research will concentrate on using signal analysis to maximize signal-to-noise ratio for these optical measurements. In addition, the tracers and instrumentation will be tested by comparison to existing multiple indicator techniques which rely on radioisotope tracer methods. The research should lead to the development of reliable, new instrumentation for the acquisition and analysis of nonradioactive multiple indicator dilution studies which can evaluate microcirculatory status of the lungs in intact animals and patients. This system should be applicable to the physiological assessment of the respiratory variables of capillary permeability and other microcirculatory parameters in Adult Respiratory Distress Syndrome patients. Further, the method should be useful in experimental studies of the lung circulation. Successful completion of the research should allow the numbers of animals required for testing hypotheses on vascular permeability to be significantly reduced.